We have all heard tragic stories of young high school or college athletes dying from cardiac arrest during a practice or game. When this happens, it is often the result of an underlying condition called arrhythmogenic cardiomyopathy (commonly called ARVC because of its effect on the heart’s right ventricle). Often, these individuals were not even aware that they had a heart condition, making these sudden heart-related deaths difficult to predict.

At Geisinger, we are working to prevent these tragedies. ARVC is an inherited condition, and most cases have been linked to specific genetic causes. Knowing that a person has one of these genetic markers could therefore be a useful first step in detecting ARVC and preventing sudden cardiac death. For this reason, DNA samples from Geisinger’s MyCode® project are being systematically screened for the specific genetic risk factors associated with ARVC — among numerous other serious health conditions — as part of Geisinger’s GenomeFIRST return of results initiative. The hope is that individuals identified with an ARVC genetic marker would be notified of this risk so they can explore appropriate preventive actions. 

While this concept is straightforward, there are several important unknown factors that present a challenge. Most importantly, we don’t know how many people have these genetic markers and, of those who do, what percentage of them will develop disease. Without this appreciation, we may over- or underestimate the number of patients in need of treatment. 

In an article published last month in the journal Genetics in Medicine, Geisinger researchers, in collaboration with scientists from Johns Hopkins, Harvard, University of Kentucky and Regeneron Pharmaceuticals, took a first step to help fill these important gaps in our knowledge. Using Geisinger’s MyCode database, we found that 1 in 143 people have a variant that has been associated with ARVC in previous scientific studies. However, the evidence supporting most of these findings did not meet the current standards to be considered clinically actionable. Instead, only 1 in 1,706 people carried genetic markers that meet these standards for Geisinger’s return of results. Using data from Geisinger’s electronic health record (EHR), we found that none of these individuals had a previous diagnosis of ARVC, and there was little evidence of symptoms commonly associated with the disease. 

ARVC presents a substantial diagnostic challenge, so these EHR findings are inconclusive, but suggest that the percentage of people carrying these genetic risk factors who will develop ARVC may be low. Additionally, these findings demonstrate that genetic screening alone will not be enough to help guide clinical care for these patients, but requires complementary diagnostic techniques. State-of-the-art medical imaging, such as MRI, may help fill this need by detecting subtle changes in the heart’s structure and function. Hence, researchers in Geisinger’s Department of Imaging Science and Innovation are working to evaluate these techniques in tandem with the return of results program to prove these capabilities. With this novel combination of genetics and imaging, we hope to develop an effective model of precision medicine for our patients at risk for ARVC.

Christopher Haggerty, Ph.D., is a research scientist in the Department of Imaging Science and Innovation at Geisinger. His research focuses on integrating medical imaging, biomechanics, and cardiac genetics to improve the understanding and ability to diagnose heart disease.
For more on this subject, please contact David Stellfox in Research Communications at dbstellfox@geisinger.edu.